The goal of this work is the elucidation of the mechanisms controlling the rate of protein synthesis at the cytoplasmic level in mammalian cells, and the differences between these mechanisms in normal and malignant cells. The tissue utilized in the present studies is the Ehrlich ascites tumor cell growing in suspension culture. This cell demonstrates cytoplasmic control mechanisms which respond vigorously to alterations in nutrient (essential amino acid, glucose, or serum) concentration in the medium. We have demonstrated that upon nutrient deprival one such mechanism operates to inhibit polypeptide chain initiation by inhibiting the binding of Met-tRNAf to the native 40s ribosomal subunit. This step requires eucaryotic initiation factor 2 (eIF-2), which, together with Met-tRNAf and GTP form a ternary complex. We are presently examining factors affecting ternary complex formation. We find a soluble inhibitor of complex formation, and a soluble protein which prevents this inhibition. We are comparing the affects of these factors upon phosphorylated and unphosphorylated eIF-2. We find an eIF-2 kinase and an eIF-2 phosphatase, and are studying the extent of phosphorylation of ribosome-bound and free eIF-2 in fed and nutritionally deprived cells.